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Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care. [ABSTRACT FROM AUTHOR]

The association between prepartum time-series fetal heart rate pattern changes and cord blood gas data at delivery was examined using the conventional 5-tier classification and the Rainbow system for 229 female patients who delivered vaginally. They were classified into three groups based on the results of umbilical cord blood gas analysis at delivery. The fetal heart rate pattern classifications were based on analysis of measurement taken at 10-min intervals, beginning at 120 min pre-delivery. The relationship between fetal heart rate pattern classification and cord blood pH at delivery changed over time. The 5-tier classification at each interval increased before delivery in the Mild and Severe groups compared with the Normal group. No significant differences were observed between acidemia groups. The Rainbow classification showed a significant differences between the acidemia groups at each interval, particularly during the prepartum period. A relationship between classification and outcome was evident before delivery for both the 5-tier classification and Rainbow system. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the patterns of fetal heart rate (FHR) changes during evolving hypoxemia (low oxygen levels) in labor. The researchers found that there are multiple potential sequences of FHR changes during repetitive hypoxemia, and they hope that further research will uncover the true range of patterns and their prognostic significance. The study also found that both decreased and increased FHR variability can be indicators of fetal compromise, but the proportions of each were not provided. The authors suggest that increased FHR variability may be a more common sign in recent studies due to changes in clinical intervention. [Extracted from the article]

Purpose: To evaluate the effectiveness and safety of tadalafil treatment for hypertensive disorder of pregnancy (HDP).Materials and Methods: In an open-label, randomized clinical trial, singleton pregnancies with HDP between 20 and 33 weeks of gestation were randomized to take 20 mg oral tadalafil every day (tadalafil treatment group) or no drug (conventional treatment group). The primary outcome was prolongation of pregnancy from randomization to delivery. However, this article primarily focuses on the safety assessments performed in the tadalafil treatment for HDP population, because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide.Results: From October 2016 to March 2018, 28 patients were randomized to each group and two cases were excluded (tadalafil treatment group: 12 cases; conventional treatment group: 14 cases). The significant adverse events related to tadalafil did not occur in the tadalafil treatment group. Among maternal adverse events, specifically with regard to headaches, there were significant differences between the two groups (0% in tadalafil group versus 43% in conventional treatment group; p = .02). There was no difference in the prolongation period of pregnancy that served as primary outcomes in both the groups (17.5 d in tadalafil group versus 16.5 d in conventional group, p = .96). The significant adverse events occurred at the same frequency as between the conventional treatment group and the tadalafil treatment group. And, maternal headache decreased significantly in the tadalafil treatment group.Conclusions: Tadalafil treatment is safe for pregnant women with HDP. Moreover, tadalafil did not prolong the gestational period in pregnant women with HDP. [ABSTRACT FROM AUTHOR]

We, the Editors and Publisher of The Journal of Maternal-Fetal & Neonatal Medicine, have retracted the following article:Shoichi Magawa, Hiroaki Tanaka, Fumi Furuhashi, Shintaro Maki, Masafumi Nii, Kuniaki Toriyabe, Eiji Kondo & Tomoaki Ikeda; Intrapartum cardiotocogram monitoring between obstetricians and computer analysis, The Journal of Maternal-Fetal & Neonatal Medicine (Author Accepted Version), 10.1080/14767058.2019.1615876.The incorrect manuscript was provided by the authors resulting in a duplicate publication.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as "Retracted". [ABSTRACT FROM AUTHOR]

Background: Selective fetal growth restriction (sFGR) is a condition of twin pregnancy in which the development of one fetus is restricted, despite normal growth of the other fetus. A method of intrauterine therapy for sFGR does not currently exist. The only treatment for sFGR is to terminate the pregnancy before the FGR worsens. In twin pregnancies, maternal and intrauterine environments are common in both fetuses, thus a placental factor is considered the cause of FGR in fetuses. Tadalafil is a phosphodiesterase (PDE)-5 inhibitor that induces an increase in uterine blood flow by dilatation of blood vessels in cases of FGR with placental dysfunction, which improves FGR.Purpose: The aim of this study was to investigate the safety and maximum tolerated dose (MTD) of tadalafil administered for twin pregnancy (diamniotic-monochorionic twin or diamniotic-dichorionic twin).Methods: In this phase I, open-label, dose-escalation trial, sequential patient cohorts (3 + 3 dose-escalation design) for twin pregnancy received tadalafil (20 or 40 mg/d) as a single dose by oral administration from the day they were diagnosed with sFGR, defined as estimated fetal weight (EFW) < 3% tiles, that is, -1.8 SD the mean EFW for gestational age (GA) to unacceptable toxicity or the day of delivery. This study evaluated the safety of maternally administered tadalafil for sFGR, examining maternal, fetal, and neonatal adverse events. Maternal adverse events were graded on the basis of the Common Terminology Criteria for Adverse Events v4.0.Results: Six women with sFGR who were pregnant with twins were treated with tadalafil. There were no severe adverse events in either cohort, although the most common (≥3 patients) drug-related adverse events were headache and heart failure. The MTD of tadalafil among Japanese patients was 40 mg.Conclusions: Tadalafil has a manageable safety profile up to an MTD of 40 mg/d. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the accuracy of computer analysis and its features to be used as a fu fetal heart rate (FHR) interpretation method in clinical settings.Methods: The Trium CTG Online® was used as the computer analysis software. Twenty-six cases of intrapartum FHR tracings (total time, 6900 min) were randomly selected from third-trimester pregnancies. Three obstetricians blinded to the patients' clinical information traced the decelerations, variability, and baseline cardiotocogram (CTG) data. Three obstetrician observer individually interpreted the data and only the waveforms they interpreted were adopted. The agreement between the deceleration and baseline, variability, and level of five-tier system was estimated. Weighted kappa (κ) statistics were used to assess reliability.Results: Based on the observers and Trium's classification, κ was 0.78 and the strength of agreement level was substantial. The obstetricians and Trium mostly agreed on the variability and baseline data. However, κ of each deceleration was approximately 0.65 (0.63-0.66), with substantial strength of agreement.Conclusion: Based on the obstetricians and Trium's interpretation, the latter was found to be excellent for FHR interpretation. However, it was difficult for Trium to interpret specific waveform patterns. Therefore, clinical staff should understand these characteristics to more sensitively evaluate the fetal well-being. [ABSTRACT FROM AUTHOR]